The project aims to enable quantitative analysis of physiological processes in living cells in their natural environment—without labels, external staining, or harmful light doses—using non-damaging low-coherence (or even incoherent) illumination. Our goal is to develop a simple QPM module that can be used with any light microscope.

Label-free imaging uses various endogenous contrast mechanisms, such as intrinsic absorption, scattering, or the refractive index (RI). Well-known and widely used optical microscopy techniques that leverage cellular phase as a contrast mechanism include Zernike phase-contrast microscopy and differential interference contrast (DIC) microscopy, but they provide only qualitative information and are prone to artifacts (low image contrast and the “halo” effect). Quantitative phase microscopy (QPM) can be viewed as an extension of phase-contrast methods. QPM delivers measurable information about a sample’s phase without the need for external markers, and it has already proven useful in biomedicine. Label-free imaging is achieved thanks to the sample’s intrinsic contrast—internal structures impose different optical path delays on the transmitted light. This optical path delay is then recovered by numerically converting an interferogram into nanoscale-precise, subcellular 2D/3D/4D maps of the specimen. This non-phototoxic, non-destructive imaging approach brings biology and metrology closer together by producing quantitative maps of living biostructure (e.g., cell mass, volume, surface area, and their evolution over time), modernizing sample visualization and enabling label-free, noninvasive optical measurements that support precise diagnostics.

Principal Investigator: Piotr Zdańkowski, PhD

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